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http://dx.doi.org/10.1016/j.omtn.2025.102558 | DOI Listing |
Nat Commun
August 2025
Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Breast cancer (BC) is one of the most common cancers globally. Genetic testing facilitates screening and informs targeted risk-reduction and treatments. However, genes included in testing panels are from European-ancestry studies.
View Article and Find Full Text PDFMol Med Rep
November 2025
Lin He's Academician Workstation of New Medicine and Clinical Translation, Jining Medical University, Jining, Shandong 272067, P.R. China.
Endometrial cancer (EC) is a common gynecologic malignancy that often exhibits molecular features such as extensive somatic copy number alterations, microsatellite instability and frequent mutations, which considerably affect the physical and mental well‑being of women. The Fanconi anemia (FA) pathway is a DNA damage repair pathway involving multiple FA genes that play crucial roles in DNA damage repair as well as the maintenance of genome stability. Abnormalities in FA, such as deletions or mutations, may lead to defects in DNA damage repair, resulting in increased genomic instability and/or an abnormal cell cycle, ultimately leading to EC.
View Article and Find Full Text PDFMol Ther Nucleic Acids
June 2025
Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, NY 11568, USA.
Alternative Lengthening of Telomeres (ALT) is a telomerase-independent telomere maintenance mechanism that enables cancer cells to gain unlimited replicative capacity. ALT relies on recombination-mediated telomere elongation and is promoted by telomeric replication stress. However, ALT requires strict regulation, as excessive replication stress or recombination are cytotoxic.
View Article and Find Full Text PDFCancers maintain their telomeres through two main telomere maintenance mechanisms (TMMs): 85-90% of cancers rely on telomerase, while 10-15% of cancers adopt the Alternative Lengthening of Telomere (ALT) pathway. Previously, we and others reported that FANCM, one of the Fanconi Anemia proteins, plays a critical role in suppressing replication stress and DNA damage at ALT telomeres by actively disrupting TERRA R-loops [1-4]. Here, we showed that inactivation of DNA2 in ALT-positive (ALT+) cells, but not in telomerase-positive (TEL+) cells, induces a robust increase of replication stress and DNA damage at telomeres, which leads to a pronounced increase of many ALT properties, including telomere dysfunction-induced foci (TIFs), ALT-associated PML bodies (APBs), and C-circles.
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